基于分子网络分析的肾交感神经与RAAS crosstalk对近曲肾小管上皮细胞NHE调控机制的研究

交感神经过度激活是高血压发病的一个重要环节。研究表明，肾交感神经通过激活钠氢交换蛋白（NHE）调节肾小管钠的重吸收，肾交感神经可能通过与RAAS crosstalk作用调节肾脏NHE1和NHE3的表达。我们利用分子网络分析的方法预测肾上腺素能受体和RAAS与NHE的调节途径筛选出核心蛋白15个。通过GO分析、KEGG 通路富集分析、结合文本挖掘方法加以验证，提示这些蛋白主要参与生物学调控的进程及信号通路的传递。由此，本研究假设肾上腺素能受体/RAAS 与NHE1、NHE3间的分子网络蛋白通路参与了肾交感神经对近曲肾小管上皮细胞NHE1、NHE3表达的信号调控。我们拟通过体内和体外实验，利用细胞干预、RNA干扰技术及大鼠去肾神经术模型明确筛选出的调控途径关键蛋白在肾交感神经对近曲肾小管上皮细胞的NHE1和NHE3表达调控途径中的作用，从不同水平揭示肾交感神经对血压的调节的分子生物学机制。

Sympathetic nerve activity has an important role in developing hypertension. Studies suggested that renal sympathetic nerve adjust renal tubular reabsorption of sodium by activating sodium hydrogen exchange protein (NHE), and maybe renal sympathetic nerve regulate the expression of NHE1 and NHE3 in kidney on account of the crosstalk effects to RAAS. We previously had predicted and screened out critical proteins of the regulatory pathway between NHE and adrenergic receptor/RAAS based on the network analysis. After GO analysis, pathway enrichment, and text mining, we found that these critical proteins are involved in the biological processes related to biological regulation. It is shown that these proteins mainly involved in the transmission of signaling pathways. Therefore, we hypothesize that molecular network protein pathways between NHE1, NHE3 and adrenergic receptor/RAAS crosstalk involved in the signal transduction pathways of renal sympathetic nerve regulation on the expressions of NHE1, NHE3 in the proximal renal tubular epithelial cells. To supported our hypothesis, the present study served to assess the role of critical proteins in the regulatory pathway of renal sympathetic nerve regulation on the expressions of NHE1, NHE3 in the proximal renal tubular epithelial cells by in vitro and in vivo experiments, including cell intervention experiment, RNA interference technique, and renal denervation model in spontaneously hypertensive rats. The present study will reveal the molecular biological mechanisms of renal sympathetic regulation of blood pressure at different levels.